Interferon .alpha. and .beta. are peptides having an antineoplastic effect and an antiviral effect, and are used by intramuscular or subcutaneous injection for treating various tumors such as kidney cancer or multiple myeloma and viral diseases such as active chronic hepatitis type C Interferon .gamma. is used for treating tumors (kidney cancer). Since it also has a potent immunity controlling effect, its use for treating allergic diseases such as atopic dermatitis has been considered.
Conventional basic treatment of atopic dermatitis is external application of steroid agents and oral administration of antihistaminics or antiallergic agents. Other treatments include hyposensitization, allergen (mites, food) elimination, PUVA (psoralen long wavelength ultraviolet irradiation), and bacteria vaccine therapy. However, any of such treatments is not satisfactory. Particularly, steroid agents for external application show an immediate effect but cause side effects due to long-term continuous application, such as atrophy of skin, angiotelectasis, flush, purpura, and readily infectiosity. Recently, the treatment of atopic dermatitis is directed to therapy with cytokines whose mechanism of function is novel (Hidemi Nakagawa, Rinsho Meneki (Clinical Immunology) 27, (supple 16), 597-602 (1995), Sachiko Kobayashi et al., Rinsho Meneki (Clinical Immunology) 27, (supple 16), 603-609 (1995)). Patients with atopic dermatitis has imbalance between Th1 helper cells and Th2 helper cells. In other words, Th2 helper cells are dominant. The promising tentative theory is that increased production of cytokines such as interleukin-4 and interleukin-5 from Th2 cells promotes IgE production and differentiation, proliferation, and infiltration of phlogocytes such as eosinophilic leukocytes to thereby induce inflammation. Generally, application of an antigen to sensitized human skin, it causes skin reaction that becomes maximum immediately and 4 to 8 hours after the application and lasts 24 to 48 hours thereafter. The former reaction is called immediate reaction (associated with IgE-mast cell) and the latter is called late allergic reaction. Particularly, it is said that the late reaction is closely related to symptom of allergic diseases including asthma. The mechanism of the late reaction has not been clarified. It is now considered as late phase reaction of the type I allergy associated with IgE-mast cells and is closely connected with infiltration of eosinophilic leukocytes due to dominance of Th2 helper cells (Motohiro Kurosawa, Rinsho Meneki (Clinical Immunology) 27(5), 564-574, 1995). The balance between Th1 helper cells and Th2 helper cells are regulated by interferon. Interferon .gamma. enhances differentiation of Th0 cells to Th1 cells. Attempts have been made to use interferon .gamma., which corrects dominance of Th2 cells, for therapy of atopic dermatitis. The main interferon treatment is subcutaneous injection of recombinant interferon .gamma. (Hanifin J. M., J. Am. Dermatol. 28, 189-197, 1993, Nishioka K. et al., J. Dermatol. 22(3), 181-185, 1995). It was reported that this treatment improved skin conditions and decreased the number of eosinophilic leukocytes in blood. Since interferon has an immunity potentiating effect, it does not cause side effects of readily-infectiosity, which is often caused by treatment with steroids. However, it is expensive and causes other side effects (fervescene, cold-like symptoms, headache). Thus, it cannot be a satisfactory medicine. This is not only applied to the case that interferon is used for treating atopic dermatitis but also the case that it is used as an antiviral or an antitumor agent in the form of injection.
When interferon is administered from the outside of the body, it has still other problems. It can be expected to solve the problems of the interferon injection (cost and side effects) by topical application (external application) of a low molecular weight synthetic compound as an interferon inducer. Several interferon-inducing compounds are known. For example, the known compounds include some 1-substituted-1H-imidazo[4,5-c]quinoline-4-amine compounds, represented by 1-isobutyl-1H-imidazo[4,5-c]quinoline-4-amine (Imiquimod), which is an antiviral agent (European Patent No. 145340, U.S. Pat. No. 4,689,338, U.S. Pat. No. 4,698,348, U.S. Pat. No. 4,929,624, European Patent No. 385630, U.S. Pat. No. 5,346,905, etc.). Some of them are under clinical test as an external preparation. Since these are used to treat genital wart (Imiquimod, Pharma Projects 1996), their percutaneous absorbability is expected to be poor. They also show low interferon-inducing activity in humans.
Therefore, an objective of the present invention is to provide a novel compound that has an eosinophilic leukocyte infiltration-inhibiting effect based on a potent interferon (.alpha.,.gamma.)-inducing activity and excellent percutaneous absorbability, causes fewer side effects, and thus effective for allergic inflammatory diseases such as atopic dermatitis, various tumors, and viral diseases, and a medicinal preparation containing the same.